Many drugs modify operant behavior as a function of the non-drug baseline rate of responding: a phenomenon described as rate-dependent drug effects. A neurochemical basis for rate dependency is unknown; however, behavior per se modifies the rate of brain catecholamine metabolism, and thus a neurochemical mechanism has been demonstrated which potentially may mediate some drug X behavior interactions. Little direct information is available concerning the effect of behavior on the metabolism of other neurotransmitters. On the other hand, substantial evidence suggests that brain 5-hydroxytryptamine (5-HT) metabolism plays a crucial role in the maintenance and regulation of many behaviors, including schedule-controlled behaviors. The proposed experiments are intended to determine directly if operant behavior modifies rat brain 5-HT metabolism. Changes in metabolism of 5-HT will be determined by measuring accumulations of brain 5-hydroxyindoleacetic acid (5-HIAA) after probenecid administration. In the basic paradigm, rats will be trained to press a lever under a variable interval 30-second (VI30) schedule of food presentation. When responding is stable, probenecid is injected before the final session, all rats are killed at the end of this session, and brain parts are subsequently assayed for 6-HIAA by organic extraction and spectrophotofluorometry. The role of response rate and reinforcer consumption in modifying 5-HIAA production are tested as independent variables by manipulating parameters of the VI 30. In one experiment a paced VI 30 is used to generate different rates of responding while maintaining reinforcement density constant. In a second experiment, a reinforcer-witholding procedure is used to test the role of reinforcer consumption in modifying 5-HIAA production.